Antiproliferative Activity of Buddleja saligna (Willd.) against Melanoma and In Vivo Modulation of Angiogenesis

Funding Information: This research was funded by the University of Pretoria, the National Research Foundation-DAAD (SFD13080220333), the Department of Science and Innovation (DST/CON 0059/2019), the Innovation Hub, L’Oréal-UNESCO and FCT-MCTES (UIDP/04378/2020 and UIDB/04378/2020). Publisher Copyright: © 2022 by the authors.Melanoma cells secrete pro-angiogenic factors, which stimulates growth, proliferation and metastasis, and therefore are key therapeutic targets. Buddleja saligna (BS), and an isolated triterpenoid mixture (DT-BS-01) showed a fifty percent inhibitory concentration (IC50) of 33.80 ± 1.02 and 5.45 ± 0.19 µg/mL, respectively, against melanoma cells (UCT-MEL-1) with selectivity index (SI) values of 1.64 and 5.06 compared to keratinocytes (HaCat). Cyclooxygenase-2 (COX-2) inhibition was observed with IC50 values of 35.06 ± 2.96 (BS) and 26.40 ± 4.19 µg/mL (DT-BS-01). BS (30 µg/mL) significantly inhibited interleukin (IL)-6 (83.26 ± 17.60%) and IL-8 (100 ± 0.2%) production, whereas DT-BS-01 (5 µg/mL) showed 51.07 ± 2.83 (IL-6) and 0 ± 6.7% (IL-8) inhibition. Significant vascular endothelial growth factor (VEGF) inhibition, by 15.84 ± 4.54 and 12.21 ± 3.48%, respectively, was observed. In the ex ovo chick embryo yolk sac membrane assay (YSM), BS (15 µg/egg) significantly reduced new blood vessel formation, with 53.34 ± 11.64% newly formed vessels. Silver and palladium BS nanoparticles displayed noteworthy SI values. This is the first report on the significant anti-angiogenic activity of BS and DT-BS-01 and should be considered for preclinical trials as there are currently no US Food and Drug Administration (FDA) approved drugs to inhibit angiogenesis in melanoma.publishersversionpublishe

Green nanotechnology of MGF‑AuNPs for immunomodulatory intervention in prostate cancer therapy

Abstract Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent

Targeting acne bacteria and wound healing in vitro using Plectranthus aliciae, rosmarinic acid, and tetracycline gold nanoparticles

SUPPLEMENTARY MATERIAL : FIGURE S1: Ultraviolet-visible spectroscopy (UV-Vis) and stability studies of biosynthesised gold nanoparticles; TABLE S1: Functional groups identified with Fourier Transform Infrared Spectroscopy.DATA AVAILABILITY STATEMENT : Data is contained within the article and supplementary material.Gold nanoparticles from plant extracts and their bioactive compounds to treat various maladies have become an area of interest to many researchers. Acne vulgaris is an inflammatory disease of the pilosebaceous unit caused by the opportunistic bacteria Cutibacterium acnes and Staphylococcus epidermis. These bacteria are not only associated with inflammatory acne but also with prostheticimplant- associated infections and wounds. Studies have hypothesised that these bacteria have a mutualistic relationship and act as a multispecies system. It is believed that these bacteria form a multispecies biofilm under various conditions and that these biofilms contribute to increased antibiotic resistance compared to single-species biofilms. This study aimed to investigate the antibacterial and wound healing potential of synthesised gold nanoparticles (AuNPs) from an endemic South African plant, Plectranthus aliciae (AuNPPAE), its major compound rosmarinic acid (AuNPRA) and a widely used antibiotic, tetracycline (AuNPTET). Synthesised gold nanoparticles were successfully formed and characterised using ultraviolet–visible spectroscopy (UV–vis), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FTIR), zeta potential ( -potential), high-resolution transmission electron microscopy (HRTEM), and selected area electron diffraction (SAED), and they were investigated for stability under various biological conditions. Stable nanoparticles were formed with -potentials of 18.07 0.95 mV (AuNPPAE), 21.5 2.66 mV (AuNPRA), and 39.83 1.6 mV (AuNPTET). The average diameter of the AuNPs was 71.26 0.44 nm, 29.88 3.30 nm, and 132.6 99.5 nm for AuNPPAE, AuNPRA, and AuNPTET, respectively. In vitro, biological studies confirmed that although no antibacterial activity or biofilm inhibition was observed for the nanoparticles tested on the multispecies C. acnes and S. epidermis systems, these samples had potential wound closure activity. Gold nanoparticles formed with rosmarinic acid significantly increased wound closure by 21.4% at 25% v/v ( 29.2 g/mL) compared to the negative cell control and the rosmarinic acid compound at the highest concentration tested of 500 g/mL. This study concluded that green synthesised gold nanoparticles of rosmarinic acid could potentially be used for treating wounds.The National Research Foundation of South Africa and the Department of Science and Innovation of the Republic of South Africa.https://www.mdpi.com/journal/pharmaceuticalsam2023Plant Production and Soil Scienc

Toxicity Investigations of (R)-3-Hydroxybutyrate Glycerides In Vitro and in Male and Female Rats

TCN006, a formulation of (R)-3-Hydroxybutyrate glycerides, is a promising ingredient for enhancing ketone intake of humans. Ketones have been shown to have beneficial effects on human health. To be used by humans, TCN006 must be determined safe in appropriately designed safety studies. The results of a bacterial reverse mutation assay, an in vitro mammalian micronucleus study, and 14-and 90-day repeat dose toxicity studies in rats are reported herein. In the 14- and 90-day studies, male and female Wistar rats had free access to drinking water containing 0, 75,000, 125,000 or 200,000 ppm TCN006 for 92 and 93 days, respectively. TCN006 tested negative for genotoxicity and the no observed adverse effect level (NOAEL) for toxicity in the 14- and 90-day studies was 200,000 ppm, the highest dose administered. In the longer term study, the mean overall daily intake of TCN006 in the 200,000 ppm groups was 14,027.9 mg/kg bw/day for males and 20,507.0 mg/kg bw/day for females. At this concentration, palatability of water was likely affected, which led to a decrease in water consumption in both males and females compared to respective controls. This had no effect on the health of the animals. Although the rats were administered very high levels of (R)-3-Hydroxybutyrate glycerides, there were no signs of ketoacidosis

The State of the Art of Theranostic Nanomaterials for Lung, Breast, and Prostate Cancers

The synthesis and engineering of nanomaterials offer more robust systems for the treatment of cancer, with technologies that combine therapy with imaging diagnostic tools in the so-called nanotheranostics. Among the most studied systems, there are quantum dots, liposomes, polymeric nanoparticles, inorganic nanoparticles, magnetic nanoparticles, dendrimers, and gold nanoparticles. Most of the advantages of nanomaterials over the classic anticancer therapies come from their optimal size, which prevents the elimination by the kidneys and enhances their permeation in the tumor due to the abnormal blood vessels present in cancer tissues. Furthermore, the drug delivery and the contrast efficiency for imaging are enhanced, especially due to the increased surface area and the selective accumulation in the desired tissues. This property leads to the reduced drug dose necessary to exert the desired effect and for a longer action within the tumor. Finally, they are made so that there is no degradation into toxic byproducts and have a lower immune response triggering. In this article, we intend to review and discuss the state-of-the-art regarding the use of nanomaterials as therapeutic and diagnostic tools for lung, breast, and prostate cancer, as they are among the most prevalent worldwide